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Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

Neural Regeneration Research 2013年第13期8卷 1201-1209页

作者： Yi Li Xuming Hua Fang Hua Wenwei Mao Liang Wan Shiting Li Department of Neurosurgery Xinhua Hospital Shanghai Jiao Tong University School of Medicine Department of Emergency Medicine Brain Research Laboratory Emory University School of Medicine laboratory of microbiology and biochemical pharmaceutics School of Pharmacy Shanghai Jiao Tong University

Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.

关键词： neural regeneration brain injury cerebral ischemia seed cells bone marrow transplantation bonemarrow cells bone marrow regenerative cells vascular regeneration factor brain neuroregeneration

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Time-dependence of cardiomyocyte differentiation disturbed by peroxi-some proliferator-activated receptor a inhibitor GW6471 in murine embryonic stem cells in vitro

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Acta Pharmacologica Sinica 2007年第5期28卷 634-642页

作者： Ling DING Xing-guang LIANG Yi-jia LOU Institute of Pharmacology and Toxicology and biochemical pharmaceutics,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China Institute of Pharmacology and Toxicology and biochemical pharmaceutics College of Pharmaceutical Sciences Zhejiang University Hangzhou China

Aim:To investigate the possible roles of peroxisome proliferator-activated recep-tor α(PPARα) and the signal pathway regulating the transcription of PPARα inthe cardiomyocyte differentiation course of murine embryonic stem (ES) cells ***:The expression of PPARα during cardiomyocyte differentiationwas analyzed using both Western blotting and *** genes and sarcomeric proteins were evaluated when embryoid bodieswere challenged with PPARα specific inhibitor GW6471 at different time *** phosphorylation of p38 mitogen-activated protein kinase (MAPK) was stud-ied in the differentiation process,and its specific inhibitor SB203580 was em-ployed to study the function of p38 MAPK on cardiac differentiation and theexpression of PPARα.Results:The expression of PPARα was observed to be ata low level in undifferentiated ES cells and markedly induced with the appearanceof beating *** inhibition of PPARα by its specific inhibitor GW6471(1×10-5mol/L) significantly prevented cardiomyocyte differentiation and resultedin the reduced expression of cardiac sarcomeric proteins (ie α-actinin,troponin-T)and specific genes (ie α-MHC,MLC2v) in a time-dependent *** the differ-entiation course,p-p38 MAPK was maintained at a high level from d 3 followed bya decrease from d *** inhibition of the p38 MAPK pathway by SB203580between d 3 and d 7 efficiently prevented cardiomyocyte differentiation and re-suited in the capture of the upregulation of PPARα.Conclusion:Taken together,these results showed a close association between PPARα and cardiomyocytedifferentiation in vitro,and p38 MAPK was partly responsible for the regulationof PPARα.

关键词： peroxisome proliferator-activated receptor α p38 MAPK embryonic stem cells cardiomyocytes differentiation

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Icariin promotes expression of PGC-1α,PPARα,and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro

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Acta Pharmacologica Sinica 2007年第10期28卷 1541-1549页

作者： Ling DING,Xing-guang LIANG,Dan-yan ZHU,Yi-jia LOU~2Institute of Pharmacology and Toxicology and biochemical pharmaceutics,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China Institute of Pharmacology and Toxicology and biochemical pharmaceutics College of Pharmaceutical Sciences Zhejiang University Hangzhou China

Aim:To investigate the effect of icariin on the expression of peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1 α),peroxisome proliferator-activated receptor alpha (PPARα),and nuclear respiratory factor 1 (NRF-1) oncardiomyocyte differentiation of murine embryonic stem (ES) cells in ***:The cardiomyocytes derived from murine ES cells were verified byimmunocytochemistry using confocal laser scanning ***-specific sarcomeric proteins (ie α-actinin,troponin T) were evaluated when em-bryoid bodies (EB) were treated with icariin or retinoid *** expression ofPGC-1α,PPARα,and NRF-1 were analyzed using both semiquantitative RT-PCRand Western blotting in cardiomyocyte *** phosphorylation ofthe p38 mitogen-activated protein kinase (MAPK) was studied in the differentia-tion process,and its specific inhibitor SB203580 was employed to confirm thefunction of the p38 MAPK on icariin-induced cardiac ***:The application of icariin significantly induced the cardiomyocyte differentiationof EB as indicated by the promoted expression of α-actinin and troponin *** of PGC-1α,PPARα,and NRF-1 increased coincidently in early differ-entiation and the increase was dose-dependently upregulated by icariin *** phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8,andthe activation was further enhanced and prolonged when the EB were subjectedto icariin,which was concurrent with the elevation of PGC-1α,PPARα,and ***,the inhibition of the p38 MAPK pathway by SB203580 efficientlyabolished icariin-stimulated cardiomyocyte differentiation and resulted in the cap-ture of the upregulation of PGC-1α,PPARα,and ***:Takentogether,icariin promoted the expression of PGC-1α,PPARα,and NRF-1 duringcardiomyocyte differentiation of murine ES cells in vitro and the effect was partlyresponsible for the activation of the p38 MAPK.

关键词： icariin PGC-lα PPARα NRF-1 mitochondrial cardiomyocytes embryonic stem cells differentiation

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The immunological underpinnings of vaccinations to prevent cvtomegalovirus disease

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Cellular & Molecular Immunology 2015年第2期12卷 170-179页

作者： A. Louise McCormick Edward S. Mocarski laboratory of biochemical Pharmacology Department of Pediatrics Emery University Atlanta GA USA Department of microbiology and Immunology and Emery Vaccine Center Emery University Atlanta GA USA

A universal cytomegalovirus （CMV） vaccination promises to reduce the burden of the developmental damage that afflicts up to 0.5% of live births worldwide. An effective vaccination that prevents transplacental transmission would reduce CMV congenital disease and CMV-associated still births and leave populations less susceptible to opportunistic CMV disease. Thus, a vaccination against this virus has long been recognized for the potential of enormous health-care savings because congenital damage is life-long and existing anti-viral options are limited. Vaccine researchers, industry leaders, and regulatory representatives have discussed the challenges posed by clinical efficacy trials that would lead to a universal CMV vaccine, reviewing the links between infection and disease, and identifying settings where disrupting viral transmission might provide a surrogate endpoint for disease prevention. Reducing the complexity of such trials would facilitate vaccine development. Children and adolescents are the targets for universal vaccination, with the expectation of protecting the offspring of immunized women. Given that a majority of females worldwide experience CMV infection during childhood, a universal vaccine must boost natural immunity and reduce transmission due to reactivation and re-infection as well as primary infection during pregnancy. Although current vaccine strategies recognize the value of humoral and cellular immunity, the precise mechanisms that act at the placental interface remain elusive. Immunity resulting from natural infection appears to limit rather than prevent reactivation of latent viruses and susceptibility to re-infection, leaving a challenge for universal vaccination to improve upon natural immunity levels. Despite these hurdles, early phase clinical trials have achieved primary end points in CMV seronegative subjects. Efficacy studies must be expanded to mixed populations of CMV-naive and naturally infected subjects to understand the overall

关键词： congenital disease prevention re-infection vaccine

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Preliminary investigations into surface molecularly imprinted nanoparticles for Helicobacter pylori eradication

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Acta Pharmaceutica Sinica B 2015年第6期5卷 577-582页

作者： Jiaying Han Yinjing Sun Jiapeng Hou Yuyan Wang Yu Liu Cao Xie Weiyue Lu Jun Pan Department of pharmaceutics School of PharmacyFudan University Key laboratory of Smart Drug Delivery (Fudan University) Ministry of Education Department of microbiology Shanghai Medical CollegeFudan University

This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles(SMINs) designed to adhere to Helicobacter pylori(***).Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method.A fraction of Lpp20,an outer membrane protein of *** known as NQA,was chosen as template and modified with myristic acid to facilitate its localization on the surface of the *** interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance(SPR),change in zeta potential and fluorescence polarization(FP).The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control *** vitro experiments also indicate that such SMINs are able to adhere to *** and may be useful for *** eradication.

关键词： Surface molecularly imprinted nanoparticles Epitope imprinting NQA Lpp20 Helicobacter pylori binding

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Applications of protein engineering in the microbial synthesis of plant triterpenoids

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Synthetic and Systems Biotechnology 2023年第1期8卷 20-32页

作者： Yan Luo Yaozhu Jiang Linhao Chen Chun Li Ying Wang Key laboratory of Medical Molecule Science and pharmaceutics Engineering Institute of Biochemical EngineeringSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijingChina Key laboratory for Industrial Biocatalysis Ministry of EducationDepartment of Chemical EngineeringTsinghua UniversityBeijingChina

Triterpenoids are a class of natural products widely used in fields related to medicine and health due to their biological activities such as hepatoprotection,anti-inflammation,anti-viral,and *** the advancement in biotechnology,microorganisms have been used as cell factories to produce diverse natural *** the significant progress that has been made in the construction of microbial cell factories for the heterogeneous biosynthesis of triterpenoids,the industrial production of triterpenoids employing microorganisms has been stymied due to the shortage of efficient enzymes as well as the low expression and low catalytic activity of heterologous proteins in *** engineering has been demonstrated as an effective way for improving the specificity,catalytic activity,and stability of the enzyme,which can be employed to overcome these *** review summarizes the current progress in the studies of Oxidosqualene cyclases(OSCs),cytochrome P450s(P450s),and UDP-glycosyltransferases(UGTs),the key enzymes in the triterpenoids synthetic *** main obstacles restricting the efficient catalysis of these key enzymes are analyzed,the applications of protein engineering for the three key enzymes in the microbial synthesis of triterpenoids are systematically reviewed,and the challenges and prospects of protein engineering are also discussed.

关键词： Oxidosqualene cyclase Cytochrome P450 UDP-Glycosyltransferase Triterpenoids Protein engineering

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Facile synthesis of enzyme functional metal-organic framework for colorimetric detecting H_2O_2 and ascorbic acid

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Chinese Chemical Letters 2017年第5期28卷 1006-1012页

作者： Cunji Gao Hongmei Zhu Jia Chen Hongdeng Qiu Key laboratory of Chemistry of Northwestern Plant Resources Key Laboratory for Natural Medicine of Gansu ProvinceLanzhou Institute of Chemical PhysicsChinese Academy of Sciences Institute of microbiology and biochemical Pharmacy School of PharmacyLanzhou University

In this work,a metal-organic frameworks material MIL-88 was prepared easily using solvent-thermal method,and was first found to have catalytic activities similar to those of biological enzymes such as catalase and *** material was characterized by XRD,SEM,TEM,EDX,FT-IR techniques and an N2 adsorption *** exhibited peroxidase-like activity through catalytic oxidation of the peroxidase substrate 3,3＇,5,5＇-tetramethylbenzidine（TMB） in the presence of H2O2,producing a blue-colored *** optimal conditions,the absorbance at 652 nm is linearly correlated with the concentration of H2O2 from 2.0×10^-6 mol/L to 2.03×10^-5 mol/L（R-2=0.981） with a detection limit of 5.62×10^-7 mol/L（S/N=3）.More importantly,a sensitive and selective method for ascorbic acid detection was developed using this material as a *** analytical method for ascorbic acid detection was observed to have a linear range from 2.57×10^-6 mol/L to 1.01×10^-5 mol/L（R-2=0.989） with a detection limit of 1.03×10^-6 mol/L（S/N=3）.This work suggests MOFs have advantages of preparing biomimetic catalysts and extends applications of the functional MOFs in the field of biosensor.

关键词： Metal-organic frameworks Horseradish peroxidase H2O2 Ascorbic acid Colorimetric detection Biomimetic catalyst

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Synthesis and Characterization of Carboxyl-terminated Polyethylene Glycol Functionalized Mesoporous Silica Nanoparticles

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Journal of Wuhan University of Technology(Materials Science) 2018年第6期33卷 1540-1545页

作者： WANG Yu LIU Mingxing Key laboratory of Fermentation Engineering (Ministry of Education) Hubei Provincial Cooperative Innovation Center of Industrial Fermentation National "111" Center for Cellular Regulation and Molecular Pharmaceutics Hubei Key Laboratory of Industrial MicrobiologyHubei University of Technology

Colloidal mesoporous silica nanoparticles functionalized with carboxy-terminated polyethylene glycol(CMS-PEG-COOH) were successfully synthesized by covalently grafting dicarboxy-terminated polyethylene glycol(HOOC-PEG-COOH) on the surface of the amino functionalized CMS nanoparticles with amide bond as a cross linker. Moreover, the structural and particle properties of CMS-PEG-COOH were characterized by nuclear magnetic resonance spectroscopy(1 H-NMR), transmission electron microscopy(TEM), dynamic light scattering(DLS), nitrogen adsorption-desorption measurements, X-ray diffraction(XRD), and Fourier transform infrared spectroscopy(FT-IR). The nanomaterials presented a relatively uniform spherical shape morphology with diameters of about 120 nm,and favorable dispersibility in weak acid solution. The CMSPEG-COOH exhibited no changes in the state of amorphous, while the mesopores sizes of 5.25 nm might provide the nanomaterials with large capacity for the loading and releasing of drugs. So the results indicated that CMSPEG-COOH might be a critical nanomaterial for drug delivery system in the future.

关键词： mesoporous silica nanoparticles polyethylene glycol functionalization carboxy-terminated synthesis

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Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury

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Neuroscience Bulletin 2015年第5期31卷 527-540页

作者： Lijuan Cao Jieyu Chen Mei Li Yuan-Yuan Qin Meiling Sun Rui Sheng Feng Han Guanghui Wang Zheng-Hong Qin Department of Pharmacology and laboratory of Aging and Nervous Diseases Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases College of Pharmaceutical Science Soochow University Institute of Pharmacology Toxicology and Biochemical Pharmaceutics Zhejiang University Department of Pharmacology and laboratory of Molecular Neuropathology Soochow University School of Pharmaceutical Science

In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator（TIGAR） protects neurons against ischemic brain *** the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic *** found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged *** TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after ***-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old *** expression also increased in response to oxygen glucose deprivation（OGD）/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages（E16 and E20）.The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative *** TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative *** mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation *** of cultured neurons with nicotinamide adenine dinuclectide phosphate（NADPH） significantly reduced ischemic *** results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.

关键词： TIGAR NADPH ischemia OGD H2O2

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Effects of Combined Treatment with Sansanmycin and Macrolides on Pseudomonas aeruginosa and Formation of Biofilm

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Biomedical and Environmental Sciences 2009年第2期22卷 170-177页

作者： YUE LI YUN-YING XIE RU-XIAN CHEN HONG-ZHANG XU GUO-JI ZHANG JIN-ZHE LI AND XIAO-MIAN LI Department of microbiology Tianjin Medical University Tianjin 300070 China Department of microbiology and biochemical Pharmacy Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences Beijing 100050 China

Objective To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm. Methods Micro-dilution method was used to determine the minimal inhibitory concentrations （MICs） of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PAl and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PAl and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin. Results The MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PAl and PA27853 strains through biofilms. PAl and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin. Conclusion Sub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.

关键词： Sansanmycin Macrolides Pseudomonas aeruginosa Biofilm

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